Clinical implications of human papillomavirus genotype in cervical adeno-adenosquamous carcinoma.

BACKGROUND: Our aims were to evaluate the genotype distribution of human papillomavirus (HPV) and the correlation between HPV parameters and clinicopathological/treatment variables with prognosis in cervical adeno-adenosquamous carcinoma (AD/ASC). PATIENTS AND METHODS: Consecutive patients who received primary treatment for cervical AD/ASC International Federation of Gynecology and Obstetrics (FIGO) stages I-IV between 1993 and 2008 were retrospectively reviewed. Prognostic models were constructed and followed by internal validation with bootstrap resampling. RESULTS: A total of 456 AD/ASC patients were eligible for HPV genotyping, while 452 were eligible for survival analysis. HPV18 was detected in 51.5% and HPV16 in 36.2% of the samples. Age >50 years old, FIGO stages III-IV and HPV16-negativity were significantly related to cancer relapse, and age >50, FIGO stages III-IV, HPV16-negativity and HPV58-positivity were significant predictors for cancer-specific survival (CSS) by multivariate analyses. HPV16-positivity was also significantly associated with good prognosis in those receiving primary radiotherapy or concurrent chemoradiation (RT/CCRT) (CSS: hazard ratio 0.41, 95% confidence interval 0.21-0.78). Patients with FIGO stages I-II and HPV16-negative AD/ASC treated with primary RH-PLND had significantly better CSS (p<0.0001) than those treated with RT/CCRT. CONCLUSIONS: Age >50 years old, FIGO stages III-IV and HPV16-negativity were significant poor prognostic factors in cervical AD/ASC. Patients with HPV16-negative tumour might better be treated with primary surgery (e.g. radical hysterectomy for stages I-II and pelvic exenteration for stage IVA). Those with unresectable HPV16-negative tumour (stage IIIB) should undergo CCRT in combination with novel drugs. The inferences of a single-institutional retrospective study require prospective studies to confirm.

Long-term follow up of cervical cancer patients with unexplained squamous cell carcinoma antigen elevation after post-therapy surveillance using positron emission tomography.

AIM: We aimed to define the long-term follow-up results in cervical cancer patients with unexplained squamous cell carcinoma antigen (SCC-Ag) elevation (negative conventional imaging studies, computed tomography or magnetic resonance imaging) after definitive treatment using positron emission tomography (PET). METHODS: Of the 27 women with unexplained SCC-Ag elevation, 13 died or were alive with disease (12 PET true-positive, one PET false-negative) in our previous report. In this study, we reported long-term follow-up results for all the 14 patients remaining cancer-free at cut-off of our previous analysis (seven with true-negative PET and two with false-positive PET, and five with true-positive PET having received successful curative salvage therapy). RESULTS: The seven patients with true-negative PET studies remained recurrence-free (median follow up, 70 months; range, 11-84). Two patients had pelvic inflammatory disease; their SCC-Ag levels returned to the normal range after eradication of infection. Two other patients had recurrent cystitis, and their SCC-Ag levels normalized at 5 and 36 months, respectively. The two patients with false-positive PET/computed tomography were disease-free 73.5 and 70 months from original PET studies, respectively. In contrast, of the five patients with successful salvage, two are alive without disease (at 80 and 86.7 months), one died of radiation cystitis at 54 months, and two died of their cancer subsequent to previous analysis. CONCLUSION: Cystitis or pelvic inflammatory disease may cause unexplained elevation of SCC-Ag after definitive treatment. A negative PET study usually indicates absence of disease. PET is a useful tool to identify curable recurrences, especially when SCC-Ag < 4 ng/mL.

Whole-body biodistribution and radiation dosimetry of 18F-FP-(+)-DTBZ (18F-AV-133): a novel vesicular monoamine transporter 2 imaging agent.

UNLABELLED: Vesicular monoamine transporter 2 (VMAT2) is highly expressed in the endocrine cells and brain. We investigated the biodistribution and radiation dosimetry of (2R,3R,11bR)-9-(3-(18)F-fluoropropoxy)-3-isobutyl-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-ol ((18)F-FP-(+)-dihydrotetrabenazine [DTBZ] or (18)F-AV-133), a potential VMAT2 imaging agent showing encouraging results in humans, to facilitate its future clinical use. METHODS: Nine healthy human subjects (mean age +/- SD, 58.6 +/- 4.2 y) were enrolled for the whole-body PET scan. Serial images were acquired for 3 h immediately after a bolus injection of 390.7 +/- 22.9 MBq of (18)F-AV-133 per individual. The source organs were delineated on PET/CT images. The OLINDA/EXM application was used to determine the equivalent dose for individual organs. RESULTS: The radiotracer did not show any noticeable adverse effects for the 9 subjects examined. The radioactivity uptake in the brain was the highest at 7.5% +/- 0.6% injected dose at 10 min after injection. High absorbed doses were found in the pancreas, liver, and upper large intestine wall. The highest-dosed organ, which received 153.3 +/- 23.8 microGy/MBq, was the pancreas. The effective dose equivalent and effective dose for (18)F-AV-133 were 36.5 +/- 2.8 and 27.8 +/- 2.5 microSv/MBq, respectively. These values are comparable to those reported for any other (18)F-labeled radiopharmaceutical. CONCLUSION: (18)F-AV-133 is safe, with appropriate biodistribution and radiation dosimetry for imaging VMAT2 sites in humans.

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

PURPOSE: The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. METHODS: In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. RESULTS: In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. CONCLUSION: [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application.

(18)F-FDG PET in stage IB/IIB cervical adenocarcinoma/adenosquamous carcinoma.

PURPOSE: The diagnostic and prognostic value of (18)F-FDG PET in cervical adenocarcinoma/adenosquamous carcinoma (AC/ASC) is unclear. The aim of this study was to assess the value of PET in the management of cervical AC/ASC. METHODS: Patients with resectable FIGO stage IB/IIB cervical AC/ASC receiving a preoperative MRI scan and a PET or PET/CT scan before radical surgery were eligible. Diagnostic efficacy was compared by receiver operating characteristic (ROC) analysis. Correlations between clinicopathological parameters and outcome and maximum standardized uptake values (SUVmax) of FDG uptake were evaluated. RESULTS: The study group comprised 83 patients (mean age 48.3 + or - 9.7 years) Five-year overall survival was 85.5%, with a median follow-up time of 38.6 months (range 2.8-87.2 months). Pelvic lymph node (PLN) and paraaortic lymph node (PALN) metastases were seen in 32.5% and 8.4% of patients, respectively. The difference in diagnostic efficacy in identifying metastatic PALN between PET and MRI was significant (PET versus MRI, area under the curve 0.832 versus 0.607, p=0.039). SUVmax in primary tumour was correlated with LN metastasis and deep stromal invasion. Overall survival was significantly related to FIGO stage, PLN metastasis, deep cervical stromal invasion, tumour size measured by MRI, and SUVmax of the primary cervical tumour. CONCLUSION: PET provided significantly better diagnostic efficacy than MRI in detecting PALN metastasis. Poor prognostic factors in cervical AC/ASC were SUVmax of the primary cervical tumour >5.3, stage IIB, deep cervical stromal invasion, tumour size measured by MRI > or = 40 mm, and PLN metastasis.